Pruritus is a condition involving localized or general itching. Although usually occurring in the skin, pruritus can also occur in non-cutaneous sites such as mucous membranes. A variety of causes for the condition of pruritus are known including external and endogenous causes, localized skin disorders and systemic diseases. For example, many systemic and skin diseases are accompanied by persistent or recurrent itch attacks. Itch can also be produced by a variety of chemical, mechanical, thermal and electrical stimuli.
Research into the causes of and treatment of pruritus has been limited by lack of animal models and low numbers of patients. Treatment involves diagnosis of the underlying condition that causes the pruritus and intervening therapeutically to alleviate that condition. For example, developments leading to antipruritic drugs have been, for the most part, a bonus of antiinflamatory drugs. Such treatments are not considered to be direct treatments of the pruritus and are of limited efficiacy, only occasionally and indirectly relieving the itching. In many cases, however, either the underlying cause for the pruritic condition cannot be determined or cannot be eliminated. In such cases, the direct treatment of the pruritic condition is required.
Currently available treatment modalities for pruritus include nonspecific topical agents such as emollients and counterirritants, topical and oral drugs such as steroids, local anesthetics and antihistamines, and physical modalities such as ultraviolet phototherapy and thermal stimulation. Some of these treatments are effective in pruritic conditions of a particular etiology, while others may show general but nonspecific benefit. It is also known that although many corticosteroids, e.g., hydrocortisone, fluocinide, betamethasone valerate, fluocinolene acetonide, triamcinolone acetonide and others, have antiprutitic properties, prolonged use of such corticosteroids is associated with both cutaneous and systemic toxic side effects (e.g., fluid and electrolyte disturbances, impaired wound healing, musculoskeletal, gastrointestinal, neurological and endocrine disturbances) and their widespread use is limited without medical supervision. In any event, remission of the pruritus is often slow and frequently incomplete.
Nonspecific topical preparations can act as moisturizing lotions or creams or as oil-based ointments that are occlusive and serve to soften dry skin as well as provide a protective layer. While such preparations may have valuable moisturizing and skin softening properties, they also possess undesirable effects in that they generally impart to the skin an uncomfortable feeling of warmth in addition to a sticky, oily, greasy or waxy feel. More importantly, these materials alone have little effect, if any, on reducing itching.
Topical formulations containing pharmacologically active agents are often useful in particular pruritic conditions but many may not be generally useful in all pruritic conditions. For example, topical corticosteroids are not indicated for symptomatic treatment unless a steroid responsive disorder is diagnosed.
Thus, there is a continuing need for development of new and improved, nontoxic antipruritic agents that are effective in treating pruritus resulting from a wide variety of causes or that alleviate pruritus produced by causes different than those that can be treated by currently available agents.